Our overall objective is the better understanding of the effects of alcohol on liver and intestinal cells, especially the results of chronic alcohol administraton using primarily the rat as the experimental animal. When possible human liver cells will also be studied using tissue culture systems. We will study the effects of alcohol on liver mitochondria since there is much to suggest that this organelle is directly or indirectly involved in the enchancement of alcohol metabolism as a result of chronic alcohol ingestion. Studies will include mitrochondrial enzymes, investigation of changes in mitochondrial permeability as well as mitochondrial turnover after chronic alcohol administration. These studies will also include observations on human liver cells maintained and grown in two types of tissue culture systems, namely, a monolayer and a perfusion system. We hope to demonstrate in these systems the alcohol concentrations and time needed to produce increased ethanol metabolism and to examine the biochemical mechanisms involved. We will also study agents which may speed alcohol metabolism other than alcohol; these will include studies on alanine, glycolate, urate and artificial electron mediators. Finally, we will examine the effects of alcohol on intestinal transport using isolated cells and vesicles derived from microvillus and basolateral membranes. We will also study the effects of alcohol on various enzymes related to transport as well as the effect on villus crypt cell structure and function.